Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition

Abstract

various biological roles, including transepithelial transporting fluids and nutrients, constituting the outer blood-retinal barrier, phagocytosing photoreceptor outer segment tips, and recycling bleached visual pigments. [1] Therefore, RPE dysfunction could contribute to various ocular disorders accompanied by visual impairment and even blindness, most notably age-related macular degeneration (AMD). [2] Currently, the global prevalence of AMD in individuals aged 45 years and older is ≈8.7%. [3] Regarding AMD therapeutic options, the current anti-vascular therapeutic is limited for patients with neovascular AMD, whereas nearly no satisfactory strategies were available for non-neovascular AMD, which drives an urgent requirement to improve treatments among AMD patients. [4] The explicit etiology during the progression of AMD is not thoroughly understood. However, it has been generally accepted that detrimental oxidative stress in metabolically active RPE exerts a causative, primary impact on increased RPE vulnerability and subsequent photoreceptor cell degeneration, ultimately causing impairment of central vision or blindness. [5] Ferrous ions, as a typical source of oxidative stress, have been widely implicated in the progression of AMD. [6] In contrast to the age-matched healthy macula, higher levels of total iron in RPE cells in addition to in Bruch's membrane have been measured in the AMD-affected maculae, [7] and a more than twofold increase in iron concentration was detected in the aqueous humor of dry AMD. [8] Additionally, the excessive iron released from intraocular hemorrhage induces retinal inflammation and peroxidation of unsaturated phospholipids. [9] These studies have shown that iron toxicity and oxidative stress are closely associated with RPE death during AMD progression, suggesting that highly effective ferrous reduction provides a better platform to manage these diseases. Deferoxamine (DFO) is a typical type of iron chelator, yet it can be readily eliminated, with a plasma t 1/2 of ≈5-10 min, after intravenous injection in human subjects. [10] In addition, DFO mainly accumulates in lysosomes, [11] and protects against cells merely by chelating lysosomal iron. [12] However, iron accumulation in the RPE also involves a disruption of mitochondrial iron homeostasis, [13] implicating the limited effects of DFO on alleviating iron overload and oxidative stress-induced RPE damage. Inspiringly, it has been demonstrated that the potent Ca 2+ -substituted iron-binding Prussian blue analogue KCa[Fe III (CN) 6 ] (CaPB) can enter bacterial cells and selectively deplete intracellular iron by a simplistic Lethal oxidative stress and ferrous ion accumulation-mediated degeneration/ death in retinal pigment epithelium (RPE) exert an indispensable impact on retinal degenerative diseases with irreversible visual impairment, especially in age-related macular degeneration (AMD), but corresponding pathogenesisoriented medical intervention remains controversial. In this study, the potent iron-binding nanoscale Prussia...

Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases

“…ERG was performed as described previously [ 33 ]. To evaluate whether the hydrogel affected the visual function of mice, ERG was recorded in the mice after administration for 7 days using an Espion E3 system (Diagnosys, USA) under dim red light.…”

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

“…Ferroptosis also plays a critical role in non-neoplastic diseases including neurogenic disease (e.g. Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease) ( 6–8 ), infectious diseases ( 9 ), autoimmune diseases ( 10 ), retinal diseases ( 11 ), tissue injuries ( 12 ) and some rare disorders ( 1 ). Collectively, ferroptosis is vitally implicated in a wide variety of diseases, as well as indicative for novel approaches of disease diagnosis, treatment, and prognosis prediction.…”

Fluorescence Imaging-Incorporated Transcriptome Study of Glutathione Depletion-Enhanced Ferroptosis Therapy via Targeting Gold Nanoclusters

“…GSH depletion can directly inactivate GPX4, as GDH is a cofactor of GPX4 . In addition, studies have shown that GSH depletion and inactivation of GPX4 cause LPO generation . Therefore, MDA levels were detected in 4T1 cells as a degradation product of LPO .…”

“…49 In addition, studies have shown that GSH depletion and inactivation of GPX4 cause LPO generation. 50 Therefore, MDA levels were detected in 4T1 cells as a degradation product of LPO. 51 The results in Figure 3F suggest that higher MDA levels were observed in cells treated with TfRA-AuNCs.…”